Sunosi (solriamfetol) / Jazz, SK Bio, Uniphar, Axsome Therap, Pharmanovia - LARVOL DELTA

RECOVER-SLEEP: Platform Protocol (clinicaltrials.gov) - P2 | N=1074 | Recruiting | Sponsor: Duke University | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jul 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Sleep Disorder

PARADIGM: Progressing TAAR-1, Dopamine, and Norepinephrine in Depression Using Solriamfetol (clinicaltrials.gov) - P3 | N=346 | Completed | Sponsor: Axsome Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Mar 2025 | Trial primary completion date: Dec 2025 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Comparative Efficacy and Safety of Multiple Wake-Promoting Agents for the Treatment of Residual Sleepiness in Obstructive Sleep Apnea Despite Continuous Positive Airway Pressure: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. (PubMed, CNS Drugs) - "Among all WPAs, solriamfetol demonstrated the highest efficacy on ESS and MWT, with the latter being significant. Modafinil demonstrated the best clinician impression, albeit not statistically significant. All four WPAs were associated with a low risk of serious or adverse events."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

A Trial of Solriamfetol in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (clinicaltrials.gov) - P4 | N=44 | Completed | Sponsor: Rochester Center for Behavioral Medicine | Active, not recruiting ➔ Completed | Trial completion date: May 2024 ➔ Dec 2024 | Trial primary completion date: Mar 2024 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Fatigue • Infectious Disease

Clinical Trial of Solriamfetol for Excessive Sleepiness Related to Shift Work Disorder (clinicaltrials.gov) - P4 | N=82 | Terminated | Sponsor: Charles A. Czeisler, PhD, MD | Trial completion date: Nov 2024 ➔ Apr 2024 | Recruiting ➔ Terminated; Study was stopped due to funding limitations.

Trial completion date • Trial termination

A Study to Assess the Efficacy and Safety of Solriamfetol in Subjects With ADHD (FOCUS) (clinicaltrials.gov) - P3 | N=516 | Completed | Sponsor: Axsome Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Mar 2025

Trial completion • Trial completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Expert consensus on the diagnosis and treatment of excessive daytime sleepiness in obstructive sleep apnea (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "Surgical interventions can also be used as an adjunctive therapy to CPAP (2, B).Recommendation 6: OSA patients with EDS should make lifestyle changes, including correcting poor lifestyle habits and improving sleep hygiene, to improve nocturnal sleep quality and daytime alertness (3, B).Recommendation 7: Pharmacological wake-promoting agents may be considered, after careful clinical evaluation, in OSA patients who meet the following criteria: ① Residual EDS persists despite adequate and adherent conventional OSA therapy (including CPAP, oral appliances, and surgery) with exclusion of other EDS etiologies; ② Patients with EDS who refuse, are intolerant of, or are not compliant with conventional therapy; ③ Patients with EDS that severely impairs quality of life, interferes with work/study performance, or increases the risk of accidents (including those with actual or near-miss accidents) (expert consensus, ungraded).Recommendation 8: For patients with residual EDS despite..."

Journal • Cardiovascular • CNS Disorders • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Axsome Therapeutics Announces FOCUS Phase 3 Trial of Solriamfetol in Adults with Attention Deficit Hyperactivity Disorder (ADHD) Achieves Primary Endpoint (GlobeNewswire) - P3 | N=450 | FOCUS (NCT05972044) | Sponsor: Axsome Therapeutics, Inc. | "Demonstrated substantial and statistically significant improvement in ADHD symptoms as measured by the AISRS total score compared to placebo (p=0.039, primary endpoint, 150 mg solriamfetol); Statistically significant reduction in overall ADHD disease severity as measured by the CGI-S score compared to placebo (p=0.017, key secondary endpoint, 150 mg solriamfetol); Statistically significant rate of clinical response on the AISRS compared to placebo (p=0.024, 150 mg solriamfetol); Onset of action as early as Week 1 compared to placebo (p=0.036, AISRS, 150 mg solriamfetol); Well tolerated with safety profile generally consistent with prior solriamfetol trials; With these results in the adult population in hand, we plan to initiate a trial in pediatric patients this year."

New trial • P3 data • Attention Deficit Hyperactivity Disorder

Management options for excessive daytime sleepiness in patients with obstructive sleep apnea. (PubMed, Expert Rev Respir Med) - "Solriamfetol and pitolisant are wake-promoting agents (WPA) recently approved for use in sleepy OSA patients accepting or refusing OSA treatment...However, it is still uncertain which subgroups of patients should be treated for the symptom of EDS while maintaining a low-risk profile in terms of consequences of OSA on health. Until such data are available, use of WPA in OSA patients should be managed by Sleep Specialists."

Journal • Review • Cardiovascular • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Open-Label Safety Study of Solriamfetol in Subjects with Binge Eating Disorder (clinicaltrials.gov) - P3 | N=300 | Enrolling by invitation | Sponsor: Axsome Therapeutics, Inc.

New P3 trial • Binge Eating Disorder • CNS Disorders

Axsome Therapeutics Settles Sunosi (solriamfetol) Patent Litigation with Hikma Pharmaceuticals USA (GlobeNewswire) - "Axsome Therapeutics, Inc...today announced that it has entered into a settlement agreement with Hikma Pharmaceuticals USA, Inc. (Hikma) resolving patent litigation related to Axsome’s product Sunosi (solriamfetol). The litigation, which is pending in the United States District Court for the District of New Jersey, resulted from submission by Hikma of an Abbreviated New Drug Application to the U.S. Food and Drug Administration seeking approval to market a generic equivalent of Sunosi in the United States. Under the terms of the settlement agreement, Axsome will grant Hikma a license to sell its generic version of Sunosi beginning on or after September 1, 2040, if pediatric exclusivity is granted for Sunosi, or on or after March 1, 2040, if no pediatric exclusivity is granted, subject to FDA approval and conditions and exceptions customary for agreements of this type."

Commercial • Cataplexy • Excessive Daytime Sleepiness • Excessive Daytime Sleepiness in Narcolepsy • Narcolepsy • Obstructive Sleep Apnea • Sleep Disorder

A Twelve-week, Double-blind, Placebo-controlled, Randomized, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Solriamfetol in the Treatment of Excessive Daytime Sleepiness (EDS) in Patients with Obstructive Sleep Apnea (OSA) (clinicaltrials.gov) - P3 | N=204 | Completed | Sponsor: Ignis Therapeutics (Suzhou) Limited | Recruiting ➔ Completed

Trial completion • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Patients with obstructive sleep apnea in Germany. (PubMed, Sleep Breath) - "Most patients in this study were new to therapy. Solriamfetol was typically initiated at 37.5 mg/day; titration was common. ESS scores improved with solriamfetol treatment, and most patients self-reported improvement in EDS symptoms. Common adverse events were consistent with those reported in previous clinical trials."

Journal • Retrospective data • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Obstructive Sleep Apnea • Pain • Respiratory Diseases • Sleep Disorder

Axsome Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Anticipated Milestones - Regulatory and Commercial: AXS-14 for fibromyalgia, NDA submission (1Q 2025)....AXS-12 for narcolepsy, NDA submission (2H 2025). Clinical Trial Topline Results: Phase 3 EMERGE trial of AXS-07 in migraine in patients with inadequate response to oral CGRP inhibitors (1Q 2025); Phase 3 FOCUS trial of solriamfetol in ADHD in adults (1Q 2025); Phase 3 PARADIGM trial of solriamfetol in major depressive disorder (1Q 2025); Phase 3 ENGAGE trial of solriamfetol in binge eating disorder (2026); Phase 3 SUSTAIN trial of solriamfetol in shift work disorder (2026)."

P3 data: top line • Attention Deficit Hyperactivity Disorder • Binge Eating Disorder • Fibromyalgia • Major Depressive Disorder • Migraine • Narcolepsy

Axsome Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Auvelity net product sales were $92.6 million and $291.4 million for the fourth quarter and full year of 2024, representing 89% and 124% year-over-year growth, respectively. Auvelity net product sales for the comparable periods in 2023 were $49.0 million and $130.1 million, respectively. Sunosi net product revenues were $26.2 million and $94.3 million for the fourth quarter and full year of 2024, representing 16% and 26% year-over-year growth, respectively, which consisted of $24.7 million and $90.3 million in net products sales and $1.4 million and $4.0 million in royalty and milestone revenue associated with Sunosi sales in out-licensed territories, respectively."

Sales • Cataplexy • CNS Disorders • Depression • Excessive Daytime Sleepiness • Excessive Daytime Sleepiness in Narcolepsy • Major Depressive Disorder • Mood Disorders • Narcolepsy • Obstructive Sleep Apnea • Psychiatry • Sleep Disorder

Solriamfetol in Improving Sleep in Patients With Grade II-IV Glioma (clinicaltrials.gov) - P2 | N=2 | Terminated | Sponsor: Wake Forest University Health Sciences | N=36 ➔ 2 | Suspended ➔ Terminated; Axsome has conducted a review of the ongoing IST program and are unable to continue supporting this study

Enrollment change • HEOR • Trial termination • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • MGMT

Trends and variation in issuance of high-cost narcolepsy drugs by NHS England organisations and regions from 2019 to 2022. (PubMed, J Sleep Res) - "Volumes were converted to World Health Organisation defined daily doses, to estimate the monthly number of defined daily doses of sodium oxybate, pitolisant and solriamfetol issued by each integrated care board and region. Variations between integrated care boards and regions differ substantially by drug and route of issuance. Our findings describe substantial variation in the use of specialist narcolepsy drugs in England, and highlight the untapped potential of using large, public domain datasets to publicly review higher-cost drug prescribing."

Journal • Narcolepsy • Sleep Disorder

Evaluation of pitolisant, sodium oxybate, solriamfetol, and modafinil for the management of narcolepsy: a retrospective analysis of the FAERS database. (PubMed, Front Pharmacol) - "However, potential novel or notable ADE signals were identified through real-world pharmacovigilance analysis. It is anticipated that this paper will offer additional information regarding safe and rational medication for narcolepsy."

Journal • Retrospective data • CNS Disorders • Cognitive Disorders • Depression • Developmental Disorders • Immunology • Mental Retardation • Movement Disorders • Narcolepsy • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Restless Legs Syndrome • Sleep Apnea • Sleep Disorder • Suicidal Ideation

Results of the SHARP Study: A Randomized, Placebo-Controlled, Double-Blind, Repeated-Measures, Crossover, Phase IV Clinical Trial of the Effect of the Wake-Promoting Agent Solriamfetol on Cognitive Function in Obstructive Sleep Apnea With Excessive Daytime Sleepiness and Cognitive Impairment. (PubMed, Chest) - P4 | "SHARP demonstrated that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS."

Clinical • Journal • P4 data • Alzheimer's Disease • Cognitive Disorders • Excessive Daytime Sleepiness • Mood Disorders • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Post-marketing safety profile of solriamfetol: A real-world disproportionality analysis using FDA adverse event reporting system (FAERS) database. (PubMed, Heliyon) - "Our findings provided the post-marketing safety profile of solriamfetol, highlighting potential solriamfetol's AEs. Further researches are significant to define the causality between solriamfetol and newly identified AEs."

Adverse events • Journal • P4 data • Real-world • Real-world evidence • Excessive Daytime Sleepiness • Narcolepsy • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

SOLRIAMFETOL AND COGNITIVE FUNCTION IN OBSTRUCTIVE SLEEP APNEA WITH EXCESSIVE DAYTIME SLEEPINESS AND IMPAIRED COGNITION STRATIFIED BY PRIMARY AIRWAY THERAPY ADHERENCE: SHARP (CHEST 2024) - "Solriamfetol improved EDS and objective and subjective cognitive functioning in participants with impaired cognition associated with OSA and EDS regardless of adherence to PAP therapy. CLINICAL IMPLICATIONS: These results show that nonadherence to PAP therapy, which is common for persons with OSA, did not lead to clinically meaningful differences in the therapeutic effects of solriamfetol with regard to cognition and daytime sleepiness."

Adherence • Alzheimer's Disease • Cognitive Disorders • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Comorbidity of obstructive sleep apnea and narcolepsy: A challenging diagnosis and complex management. (PubMed, Sleep Med X) - "No studies were found concerning the treatment of EDS in double-diagnosis patients, but only case reports; these latter and the experience on patients with either NT or OSA suggest that modafinil, methylphenidate, pitolisant and solriamfetol are effective. The association with OSA is likely to be explained by the involvement of orexin in hypercapnic-hypoxic responses: a deficit of orexin may promote obstructive events during sleep. Open questions warrant further investigation, especially orexin's involvement in other sleep disorders associated with EDS, and the more appropriate treatment for the OSA-narcolepsy comorbidity."

Journal • Review • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Comparative efficacy, safety and benefit/risk of alerting agents for excessive daytime sleepiness in patients with obstructive sleep apnoea: a network meta-analysis. (PubMed, EClinicalMedicine) - "The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities. Bioprojet."

Benefit-risk assessment • Journal • Retrospective data • Cardiovascular • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Solriamfetol and CBT-I in Patients With Insomnia Disorder (clinicaltrials.gov) - P4 | N=60 | Recruiting | Sponsor: University of Pennsylvania | Trial completion date: Feb 2025 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • CNS Disorders • Fatigue • Insomnia • Sleep Disorder

SOLR-IH: Efficacy and Tolerance of Solriamfetol in Patients Affected with Idiopathic Hypersomnia. (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: University Hospital, Montpellier

New P2 trial • Sleep Disorder